Mitochondria are responsible for generating the energy required for cell activities from oxygen and ingested food. Accordingly, when mitochondria do not function properly, a cell's ability to make energy is reduced or stopped, and metabolic intermediates and toxic by-products begin to accumulate. The resulting energy shortage in cells and tissues can cause a number of problems including, but not limited to, muscle weakness and fatigue as well as problems in the heart, kidneys, eyes and endocrine system. The build up of toxic intermediates can be responsible for liver problems, muscle cramps, brain dysfunction or even greater mitochondrial damage. Furthermore, the build up of toxic intermediates can have a negative effect on mitochondrial energy production further impeding normal cellular metabolism and exacerbating the energy shortage.
Mitochondrial dysfunction (MD) presents a serious challenge to eukaryotic cells and associated tissues and organs. Suitable methods of determining metabolic function and more specifically mitochondrial function are therefore desirable.
Certain methods and substances for determining mitochondrial dysfunction that use label compounds have been described in the art. Fujibayashi et al. (U.S. Pat. No. 5,843,400) describe specific radioactive tracer agents for use in the diagnosis of hypoxia or mitochondrial dysfunction that are retained in regions of electron excess. Chang et al (Annals of the New York Academy of Sciences 1042: 76-81 (2005)) describe the use of the heart perfusion labeled compound 99 mTc-sestamibi with single photon emission computed tomography (SPECT) to look at mitochondrial function in the quadriceps muscles of patients with progressive supranuclear palsy.
Ayalew et al. (Journal of Nuclear Medicine 2002; 43:566-574) investigated the role of cellular metabolic disorders in influencing labeled compound uptake and modelled the concentration ratios of labeled compound in perfused isolated rabbit hearts.
Hyperaemic reactivity is a known method in the art for discriminating patients with endothelial dysfunction (ED) (See Arsenault, U.S. Pat. No. 6,445,945). The approach is based on the intravenous injection of a labeled compound such as Tc-99m-tetrofosmin (Tc-99m) and the simultaneous non-invasive external detection of the tracer ingress and transit into both forearms: one forearm submitted to reactive hyperemia and the other contralateral forearm serving as a non-hyperemic control. Patients with ED exhibit distinct time activity curves showing tracer ingress compared to patients without ED.
Although a link between ED and MD has been postulated in the art, the precise relationship between ED and MD remains a topic of speculation. Furthermore, given the complexity of the relationship between ED and MD, measures of ED by themselves would be expected to provide only an extremely crude and potentially inaccurate indication of the presence of MD.
Furthermore, the measurement of ED requires the control of vasoconstriction and vasodilation in order to modulate the blood flow (and O2 flow) to the tissues in the patient himself, which may be cumbersome and more costly in terms of patient management and hospital resources.
Therefore, there is a need for method of evaluating mitochondrial function and a need for a method of evaluating mitochondrial function in vitro.
Therefore, there is a need for a method of evaluating mitochondrial function in a system (or subsystem) that is independent of the endothelial function.